RPGR-Related Retinal Dystrophy in Latin America-A Collaborative Study

Abstract

Purpose: To provide the first genetic and clinical characterization of RPGR-associated inherited retinal diseases (IRDs) in Latin America and assess their genetic, clinical, and socioeconomic landscape.

Design: Multicenter, international, retrospective, observational cohort study.

Methods: Patients with genetically confirmed RPGR-IRD from Brazil, Argentina, Chile, Mexico, Colombia, and Panama were included in this study. Demographic, clinical, genetic, and socioeconomic data were collected and analyzed to characterize disease prevalence and severity, assess rate of progression, and draw genotype-phenotype correlations. A socioeconomic evaluation analyzed healthcare costs and employment.

Results: The study describes the largest cohort to date of patients with RPGR-associated IRD, with 314 individuals from 205 families carrying likely disease-causing variants. Of these, 276 individuals (88%) had retinitis pigmentosa, with a mean age of disease onset at 10.9 ± 7.6 years. Analyzed cross-sectionally at the baseline visit (age 27.3 ± 17.2 years), there was a statistically significant association between age and best-corrected visual acuity (BCVA, P < .0001, R² = 0.3). Kaplan-Meier analysis showed that more than 90% of patients would maintain binocular BCVA better than 1.0 logMAR until age 40 years, decreasing to 50% by age 57 years, and by 58 years of age 50% of patients would have discernible subfoveal ellipsoid zone. The mean age of male patients whose BCVA was 1.0 logMAR or worse in their better-seeing eye was 48.3 ± 9.5 years (median, 49 years). Fourteen previously unreported variants in RPGR are described. Among patients who declared employment status (n = 122), 43% reported being unemployed or in part-time employment due to their visual impairment; among those who reported mental health well-being (n = 133), 45% reported depression or anxiety.

Conclusions: This study provides the first genetic and clinical characterization of RPGR-IRD in Latin America, contributing previously unreported variants, natural history details, genotype-phenotype correlations, and an estimated regional prevalence. By providing data on potentially eligible patients, their clinical status, and the socioeconomic impact of RPGR-IRDs, this study lays the foundation for potential access to RPGR future therapies in Latin America.